The liver is a vital organ in various vertebrates and some other animals. In the human body, the liver is the largest internal organ and provides many essential functions, including metabolic, exocrine and endocrine functions. The liver is necessary for survival. Without liver function, a human can only survive up to 24 hours. Currently, there is no way to compensate for long term absence of liver function, although liver dialysis can be used short term.
Disorders of the liver, including liver failure and end-stage liver diseases, are responsible for a huge number of deaths around the world and are a major burden on the health care system. Although liver transplantation has been successfully used for treat the disorders, its efficacy is limited and connected to many complications such as infection or rejection. Liver transplantation is also limited due to shortage of available donor organs and lifelong use of immunosuppression in recipients. Cell-based therapy, such as those based hepatocytes, on are believed to hold a great promise for treating these severe diseases.
Hepatocytes, the principal cell type in the liver, are responsible for function and regeneration of the adult liver. Along with biliary epithelial cells, hepatocytes are derived from the embryonic endoderm. Human hepatocytes can be used for modeling and understanding liver diseases, drug efficacy and toxicity testing, and cell replacement therapy. However, primary human hepatocytes are scarce and, despite their ability to efficiently proliferate in vivo, cannot be expanded in vitro.
Thus, there is a continuing unmet need for an unlimited source of human hepatocytes or hepatocyte-like cells.